31065-94-8Relevant academic research and scientific papers
Biological Efficacy and Toxicity of Diamidines in Myotonic Dystrophy Type 1 Models
Siboni, Ruth B.,Bodner, Micah J.,Khalifa, Muhammad M.,Docter, Aaron G.,Choi, Jessica Y.,Nakamori, Masayuki,Haley, Michael M.,Berglund, J. Andrew
, p. 5770 - 5780 (2015/08/24)
Myotonic dystrophy type 1 (DM1) is a disease characterized by errors in alternative splicing, or "mis-splicing". The causative agent of mis-splicing in DM1 is an inherited CTG repeat expansion located in the 3′ untranslated region of the DM protein kinase gene. When transcribed, CUG repeat expansion RNA sequesters muscleblind-like (MBNL) proteins, which constitute an important family of alternative splicing regulators. Sequestration of MBNL proteins results in the mis-splicing of its regulated transcripts. Previous work has demonstrated that pentamidine, a diamidine which is currently FDA-approved as an antiparasitic agent, was able to partially reverse mis-splicing in multiple DM1 models, albeit at toxic concentrations. In this study, we characterized a series of pentamidine analogues to determine their ability to reverse mis-splicing and their toxicity in vivo. Experiments in cell and mouse models demonstrated that compound 13, also known as furamidine, effectively reversed mis-splicing with equal efficacy and reduced toxicity compared to pentamidine.
4-Alkoxybenzamidines as new potent phospholipase A2 inhibitors
Aitdafoun, Mina,Mounier, Carine,Heymans, Francoise,Binisti, Carine,Cassian, Bon,Godfroid, Jean-Jacques
, p. 737 - 742 (2007/10/03)
A series of 4-alkoxybenzamidines was synthesized, varying the number of carbons of the alkyl chain, and their potency as phospholipase A2 (PLA2) inhibitors was evaluated. The relationship between their capacity to inhibit PLA2 activity and their lipophilicity was examined. The optimum of the inhibitory effect against two extracellular PLA2s from rabbit platelets and bovine pancreas was observed with compounds bearing an alkyl chain of 12 and 14 carbons. These 4-dodecyl and tetradecyloxybenzamidines inhibited bovine pancreatic and rabbit platelet lysate PLA2s with IC50 values of 3 μM and 5-5.8 μM, respectively. The mechanism of inhibition was of the competitive type. In addition, 4-tetradecyloxybenzamidine was shown to exert an anti-inflammatory effect in vivo on the carrageenan-induced rat paw oedema. These results show that 4-tetradecyloxybenzamidine will serve as an interesting tool to investigate the physiological role of mammalian-secreted PLA2, both in vitro and in vivo.
